{"doi":"10.1002/uog.70106","title":"Clinical significance and association with pregnancy outcome of positive non‐invasive prenatal screening for trisomy 15 in singleton pregnancy: prospective cohort study, systematic review and meta‐analysis","abstract":"<h4>Objective</h4>To investigate the incidence and clinical significance of a positive result on genome-wide non-invasive prenatal screening (NIPS) for trisomy 15.<h4>Methods</h4>We conducted a prospective cohort study of singleton pregnancies that underwent genome-wide NIPS at a single center in Hong Kong between January 2020 and April 2023. The incidence of a positive genome-wide NIPS result for trisomy 15, positive predictive value (PPV) for trisomy 15 and risk of uniparental disomy 15 (UPD15) were assessed based on cytogenetic and molecular analyses at amniocentesis. Adverse fetal outcomes were reviewed. Furthermore, a systematic review of cohort studies reporting positive trisomy 15 results from genome-wide NIPS was performed, including data from our prospective cohort. Random-effects meta-analysis was used to obtain pooled estimates of incidence and PPV. The risk of UPD15 and adverse pregnancy outcomes was also evaluated. Heterogeneity was evaluated using Higgins' I<sup>2</sup> statistic.<h4>Results</h4>In our cohort of 36 466 singleton pregnancies that underwent genome-wide NIPS, 10 (0.027%) cases were screen-positive for trisomy 15 (2.7 per 10 000 singleton pregnancies). Results from invasive diagnostic testing were available for all screen-positive cases. The PPV of genome-wide NIPS for trisomy 15 was 40.0% (4/10), and 3/10 (30.0%) cases were confirmed to have maternal UPD15. Together with our study, a total of 30 cohorts from 29 studies were included in the systematic review and meta-analysis, comprising 175 pregnancies that were screen-positive for trisomy 15. In 26 cohorts in which the total number of cases screened using NIPS were specified, the pooled incidence of trisomy 15 was 145/1 009 301 (0.013% (95% CI, 0.009-0.019%; I<sup>2</sup> = 78.4%)), or 1.3 per 10 000 singleton pregnancies. The pooled incidence was significantly higher among women screened in the first trimester compared with those tested in the second trimester. Among 102 cases with a diagnostic result from invasive testing, 22 were confirmed as having fetal trisomy 15, including eight with full trisomy 15 and 14 with true fetal mosaicism. The pooled PPV for fetal trisomy 15 was 17.4% (95% CI, 4.0-35.0%; I<sup>2</sup> = 51.5%). Among 69 cases with a result from UPD15 testing, 14 (20.3%) had maternal UPD15. Assuming that all diploid cases that did not undergo UPD15 testing had normal biparental inheritance of chromosome 15, the pooled PPV for either fetal trisomy 15 or UPD15 was 32.6% (95% CI, 14.4-53.0%; I<sup>2</sup> = 55.3%), and the residual risk of UPD15 after a fetal normal karyotype was at least 11.3%. Among patients with clinical follow-up, 68.4% experienced an adverse pregnancy outcome, including fetal loss (29.1%), termination of pregnancy (21.5%) and/or pregnancy complication (17.7%).<h4>Conclusions</h4>Although the PPV of genome-wide NIPS for fetal trisomy 15 was relatively low, a significant proportion of cases with a positive NIPS result for trisomy 15 had maternal UPD15 or fetal mosaicism, underscoring the need for diagnostic confirmation via amniocentesis. Amniocentesis should be strongly recommended for any case with a positive NIPS result for trisomy 15 to investigate UPD15 and true fetal mosaicism and guide subsequent clinical management. © 2025 International Society of Ultrasound in Obstetrics and Gynecology.","journal":"Ultrasound in Obstetrics &amp; Gynecology","year":2025,"id":2802,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.2771,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-10-21","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":31772,"name":"Y. Zheng","orcid":"0000-0002-4617-3252","position":1,"is_corresponding":false},{"id":25706,"name":"Y. Cao","orcid":"0000-0001-8747-2809","position":2,"is_corresponding":false},{"id":31773,"name":"S. W. H. Cheung","orcid":null,"position":3,"is_corresponding":false},{"id":31774,"name":"C. Y. Chung","orcid":null,"position":4,"is_corresponding":false},{"id":27185,"name":"Y. Zhao","orcid":"0000-0003-0494-6728","position":5,"is_corresponding":false},{"id":21175,"name":"X Zhu","orcid":null,"position":6,"is_corresponding":false},{"id":31775,"name":"I. F. M. Lo","orcid":null,"position":7,"is_corresponding":false},{"id":31776,"name":"H. M. Luk","orcid":null,"position":8,"is_corresponding":false},{"id":31777,"name":"Tak Yeung Leung","orcid":"0000-0002-9153-0343","position":9,"is_corresponding":false},{"id":31778,"name":"X. Kong","orcid":"0009-0009-9183-2489","position":10,"is_corresponding":false},{"id":31779,"name":"Kwong Wai Choy","orcid":"0000-0002-3616-6200","position":11,"is_corresponding":false},{"id":31780,"name":"Xue Sun","orcid":"0000-0002-9716-7549","position":12,"is_corresponding":false},{"id":17304,"name":"Yu Zheng","orcid":"0000-0002-2511-961X","position":13,"is_corresponding":false},{"id":31781,"name":"Yanwei Cao","orcid":"0000-0001-9545-0220","position":14,"is_corresponding":false},{"id":31782,"name":"Sunny Wai Hung Cheung","orcid":null,"position":15,"is_corresponding":false},{"id":31783,"name":"Yiwei Zhao","orcid":"0000-0001-8235-3739","position":16,"is_corresponding":false},{"id":31784,"name":"Xiaofan Zhu","orcid":"0000-0002-7303-1700","position":17,"is_corresponding":false},{"id":31785,"name":"Ivan F. M. Lo","orcid":"0000-0001-9059-4962","position":18,"is_corresponding":false},{"id":31786,"name":"Ho‐Ming Luk","orcid":"0000-0003-4066-4066","position":19,"is_corresponding":false},{"id":31787,"name":"Xingchen Kong","orcid":null,"position":20,"is_corresponding":false},{"id":31771,"name":"S. Xue","orcid":null,"position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":null,"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}